Tuberculin Skin Test Results Research Articles

Significance of Juvenile Idiopathic Arthritis in Pediatric-Phthisiatric Practice (Review)

Juvenile idiopathic arthritis (JIA) is a heterogeneous group that includes all forms of childhood chronic arthritis (joint inflammation lasting more than 6 weeks) of unknown cause in children under 16 years of age. JIA is the most common rheumatic disease in childhood (with an annual incidence from 1.6 to 23.0 new cases per 100,000 adolescents) and is characterized by an often hidden onset and a chronic relapsing course after diagnosis. Tuberculosis plays a special role among opportunistic infectious diseases in JIA, because rheumatic diseases are associated with an increase in the overall risk of developing tuberculosis. Children's phthisiologists often deal with the differential diagnosis difficulty of tubercular lesions of the joints with JIA, and first of all, with oligoarthritis. Clinical symptoms in JIA can be very diverse, and some characteristics of arthritis, not necessarily significant in JIA diagnosis, may have multiple etiologies that need to be carefully differentiated. It was detected during review that JIA is of urgent importance in children’s phthisiatric practice due to various reasons: oligoarthritis in JIA has similar clinical manifestations as in tuberculosis arthritis, which significantly complicates differential diagnosis and delays timely treatment of a correctly diagnosed disease; there is a high frequency of diagnosis of latent tuberculosis infection (LTBI) in JIA, which requires the appointment of preventive treatment to reduce the risk of LTBI progression to an active form of tuberculosis; patients with JIA receiving tumor necrosis factor blockers and/or methotrexate have a higher risk of tuberculosis activation, which is a serious problem in the treatment plan, and require constant monitoring for the possible development of tuberculosis. Therefore, in all pediatric patients with JIA, mandatory diagnostic screening (combination of tuberculin skin test methods with QuantiFERON®-TB Gold In-Tube, taking into account the high frequency of false-negative result of the tuberculin skin test due to immunosuppression caused by JIA) for timely detection of LTBI, and with a positive result of preventive antimycobacterial treatment, which will prevent the development of an active form of tuberculosis.Therefore, all pediatric patients with JIA should undergo mandatory diagnostic screening (combination of tuberculin skin test methods with QuantiFERON®-TB Gold In-Tube, considering the high frequency of false-negative result of tuberculin skin test due to immunosuppression caused by JIA) for timely detection of LTBI. When there is a positive result of the screening tests, it is necessary to carry out prophylactic antimycobacterial treatment, which will prevent the development of an active form of tuberculosis.

Effectiveness of preventive treatment among different age groups and Mycobacterium tuberculosis infection status: a systematic review and individual-participant data meta-analysis of contact tracing studies.

Tuberculosis is a preventable disease. However, there is debate regarding which individuals would benefit most from tuberculosis preventive treatment and whether these benefits vary in settings with a high burden and low burden of tuberculosis. We aimed to compare the effectiveness of tuberculosis preventive treatment in exposed individuals of differing ages and Mycobacterium tuberculosis infection status while considering tuberculosis burden of the settings. In this systematic review and individual-participant meta-analysis, we investigated the development of incident tuberculosis in people closely exposed to individuals with tuberculosis. We searched for studies published between Jan 1, 1998, and April 6, 2018, in MEDLINE, Web of Science, BIOSIS, and Embase. We restricted our search to cohort studies; case-control studies and outbreak reports were excluded. Two reviewers evaluated titles, abstracts, and full text articles for eligibility. At each stage, two reviewers discussed discrepancies and re-evaluated articles until a consensus was reached. Individual-participant data and a pre-specified list of variables, including characteristics of the exposed contact, the index patient, and environmental characteristics, were requested from authors of all eligible studies; contacts exposed to a drug-resistant tuberculosis index patient were excluded. The primary study outcome was incident tuberculosis. We estimated adjusted hazard ratios (aHRs) for incident tuberculosis with mixed-effects Cox regression models with a study-level random effect. We estimated the number-needed-to-treat (NNT) to prevent one person developing tuberculosis. Propensity score matching procedures were used in all analyses. This study is registered with PROSPERO (CRD42018087022). After screening 25 358 records for eligibility, 439 644 participants from 32 cohort studies were included in the individual-participant data meta-analysis. Participants were followed for 1 396 413 person-years (median of 2·7 years [IQR 1·3-4.4]), during which 2496 people were diagnosed with incident tuberculosis. Overall, effectiveness of preventive treatment was 49% (aHR 0·51 [95% CI 0·44-0·60]). Participants with a positive tuberculin-skin-test (TST) or IFNγ release assay (IGRA) result at baseline benefitted from greater protection, regardless of age (0·09 [0·05-0·17] in children younger than 5 years, 0·20 [0·15-0·28] in individuals aged 5-17 years, and 0·17 [0·13-0·22] in adults aged 18 years and older). The effectiveness of preventive treatment was greater in high-burden (0·31 [0·23-0·40]) versus low-burden (0·58 [0·47-0·72]) settings. The NNT ranged from 9 to 34 depending on age among participants with a positive TST or IGRA in both high-burden and low-burden settings; among all contacts (regardless of TST or IGRA test result), the NNT ranged from 29 to 43 in high-burden settings and 213 to 455 in low-burden settings. Our findings suggest that a risk-targeted strategy prioritising contacts with evidence of M tuberculosis infection might be indicated in low-burden settings, and a broad approach including all contacts should be considered in high-burden settings. Preventive treatment was similarly effective among contacts of all ages. None.

Differentiation of Bovine Tuberculosis and Paratuberculosis Infections with Antemortem Diagnostic Methods

In this study, based on the results of tuberculin skin tests (Bovine and Avian PPD) used in the antemortem diagnosis and differentiation of Bovine Tuberculosis, the animals in the farms with suspected Tuberculosis were serologically examined to diagnose Paratuberculosis infection and fecal bacterioscopy was performed. In addition, it was aimed to obtain data that will contribute to the eradication studies of Bovine Tuberculosis disease by comparing the antemortem diagnostic methods of Bovine Tuberculosis disease, which is endemic in Türkiye and by determining the sensitivity and specificity values of the interferon gamma (IFN-γ) test. In this context, intradermal tuberculin test was applied to 423 cattle with suspected Tuberculosis in a total of 5 dairy cattle farms, one each from Çankırı, Çorum, Ankara, Eskişehir and Konya regions, and this test was determined as the gold standard method and the sensitivity and specificity of the IFN-γ test were determined as 86% and 97%, respectively. For the diagnosis of Paratuberculosis infection, antibody ELISA, fecal bacterioscopy and IFN-γ ELISA were performed on these animals and the prevalence of these tests were 10.4%, 5.44% and 4.96% respectively and 4 (0.95%) of the cattle were positive for each of the diagnostic methods for Map infection. As a result, it was concluded that IFN-γ test, which gives similar results to intradermal tuberculin test results, can also be used in the antemortem diagnosis of Bovine Tuberculosis. Also, in the comparative intradermal tuberculin test for the diagnosis of Tuberculosis infection, avian PPD positive animals were found to play a decisive role in the detection of nonspecific reactions or Paratuberculosis infected animals, supported by other tests used for the diagnosis of Paratuberculosis.

Overlooked, dismissed, and downplayed: reversion of Mycobacterium tuberculosis immunoreactivity.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb). Following infection, immune responses to Mtb antigens can be measured using the tuberculin skin test or an interferon-γ release assay. The gain of Mtb immunoreactivity, a change from a negative to a positive tuberculin skin test or interferon-γ release assay result, is called conversion and has long been used as a measure of Mtb exposure. However, the loss of immunoreactivity (reversion; a positive followed by a negative result) has often been overlooked. Instead, in clinical and epidemiological circles, Mtb immunoreactivity is commonly considered to persist lifelong and confer a lifetime of disease risk. We present a critical review, describing the evidence for reversion from cohort studies, ecological studies and studies of TB progression risk. We outline the inconsistent reasons why reversion has been dismissed from common understanding and present evidence demonstrating that, just as conversion predominantly indicates prior exposure to Mtb antigens, so its opposite, reversion, suggests the reduction or absence of exposure (endogenous or exogenous). Mtb immunoreactivity is dynamic in both individuals and populations and this is why it is useful for stratifying short-term TB progression risk. The neglect of reversion has shaped TB research and policy at all levels, influencing clinical management and skewing Mtb infection risk estimation and transmission modelling, leading to an underestimation of the contribution of re-exposure to the burden of TB, a serious oversight for an infectious disease. More than a century after it was first demonstrated, it is time to incorporate reversion into our understanding of the natural history of TB.

Prevalence and risk factors of latent tuberculosis infection in hemodialysis patients in southwest Iran.

Tuberculosis (TB) is a significant global health concern, particularly in developing countries. Diagnosing latent tuberculosis infection (LTBI) in hemodialysis patients is crucial because of the risk of developing active tuberculosis in this population due to attenuated immune response. Herein, we assessed the prevalence of LTBI in hemodialysis patients. In this cross-sectional study, we included all patients referred to hemodialysis centers in Kohgiluyeh and Boyer-Ahmad Province, southwest Iran, in 2018 through census sampling. Tuberculin skin test (TST) was utilized to screen the patients for LTBI. All steps were done by trained physicians. In total, 183 patients (mean age: 59.3, SD= 16.0) were included in the study of which 76 (41.5%) were females, and 107 (58.5%) were males. Neither the patients nor their family members had a history of tuberculosis. Assuming an above 5-millimeter enduration as a positive TST result, 22 patients (12%) had LTBI. None of the demographic or clinical features differed between TST -negative and -positive groups. Hemodialysis patients are prone to LTBI due to several immunological and environmental factors. Screening for LTBI may be beneficial to prevent active tuberculosis in this population.

Evaluating Treatment Outcomes and Tuberculosis Infection Risks: A Comparative Study of Centralized Hospitalization vs. Home-Based Treatment.

Background: Guizhou Province in Southwest China has experimented with a centralized hospitalization (CH) treatment for active and severe cases of pulmonary tuberculosis (PTB). The objective of this study was to compare treatment outcomes of patients with tuberculosis (TB) receiving care in a CH setting with those receiving home-based (HB) care. In addition, this study aimed to assess the probability of their household contacts contracting tuberculosis infection. Method: A retrospective review of medical records was undertaken for patients with TB who completed their treatment in four counties in Guizhou, China, spanning from January 2022 to August 2023. In addition, a cross-sectional survey was conducted on the tuberculin skin test (TST) among household contacts of new patients with TB who had completed their treatment. Results: In the retrospective study, 94.8% had successful CH treatment, and 93.1% had successful HB treatment (p value = 0.70). In the prospective study, 559 and 448 household contacts of patients receiving CH treatment had 16 positive and 89 negative TST results, whereas those with HB treatment showed 26 positive and 74 negative TST results. Regarding a logistic regression analysis, the CH group was nearly two times more likely to test negative on the TST, 1.95 (95% CI: 0.98, 3.92). After adjusting for confounding variables, the odds ratio increased significantly to 4.42 (95% CI: 1.22, 16.04). Conclusions: CH for treatment of TB did not show superior success rates, but it may reduce the risk of transmitting tuberculosis infection to household contacts compared to home treatment.

Predictors of positive tuberculin skin test in neonates exposed to pulmonary tuberculosis.

Neonates are at risk of nosocomial tuberculosis (TB) infection from health care workers (HCWs) in neonatal care facilities, which can progress to severe TB diseases. Tuberculin skin test (TST) is commonly used for TB diagnosis, but its accuracy in neonates is influenced by various factors, including bacilli Calmette-Guérin (BCG) vaccination. This study aimed to identify predictors of positive TSTs in neonates exposed to HCWs with pulmonary TB. A retrospective observational study was conducted to compare the frequency of predictors between TST-positive and TST-negative neonates. Demographic, epidemiological, and clinical data of neonates exposed to TB, along with that of HCW and household contacts, were collected retrospectively through contact investigations with the Korean National TB Surveillance System (KNTSS) database. TSTs using 2 tuberculin units of purified protein derivative RT23 were performed on exposed neonates at the end of preventive TB treatment. Firth logistic regression was performed to identify predictors of TST positivity. Contact investigations revealed that 152 neonates and 54 HCWs were exposed to infectious TB index cases in 3 neonatal care facilities. Of 152 exposed neonates, 8 (5.3%) had positive TST results. Age of 6 days or more at the initial exposure is a statistically significant predictor of positive TST (Firth coefficient 2.1, 95% confidence interval 0.3-3.9, P = 0.024); BCG vaccination showed no statistical significance in both univariable and multivariable analysis. Sex, prematurity, exposure duration, duration from initial exposure to contact investigation, and isoniazid preventive treatment duration were not significant predictors. Age at the initial exposure is a significant predictor of positive TST in neonates exposed to active pulmonary TB. Given the complexities of TST interpretation, including false positives due to BCG vaccination, careful risk assessment is necessary for appropriate decision-making and resource allocation in the management of neonatal TB exposure.

Prevalence and risk factors of latent tuberculosis infection in hemodialysis patients in southwest Iran

INTRODUCTION. Tuberculosis (TB) is a significant global health concern, particularly in developing countries. Diagnosing latent tuberculosis infection (LTBI) in hemodialysis patients is crucial because of the risk of developing active tuberculosis in this population due to attenuated immune response. Herein, we assessed the prevalence of LTBI in hemodialysis patients. METHODS. In this cross-sectional study, we included all patients referred to hemodialysis centers in Kohgiluyeh and Boyer-Ahmad Province, southwest Iran, in 2018 through census sampling. Tuberculin skin test (TST) was utilized to screen the patients for LTBI. All steps were done by trained physicians. RESULTS. In total, 183 patients (mean age: 59.3, SD= 16.0) were included in the study of which 76 (41.5%) were females, and 107 (58.5%) were males. Neither the patients nor their family members had a history of tuberculosis. Assuming an above 5-millimeter enduration as a positive TST result, 22 patients (12%) had LTBI. None of the demographic or clinical features differed between TST -negative and -positive groups. CONCLUSION. Hemodialysis patients are prone to LTBI due to several immunological and environmental factors. Screening for LTBI may be beneficial to prevent active tuberculosis in this population.

Comparison of Tuberculin Skin Testing and Interferon-γ Release Assays in Predicting Tuberculosis Disease

Elimination of tuberculosis (TB) disease in the US hinges on the ability of tests to detect individual risk of developing disease to inform prevention. The relative performance of 3 available TB tests-the tuberculin skin test (TST) and 2 interferon-γ release assays (IGRAs; QuantiFERON-TB Gold In-Tube [QFT-GIT] and SPOT.TB [TSPOT])-in predicting TB disease development in the US remains unknown. To compare the performance of the TST with the QFT-GIT and TSPOT IGRAs in predicting TB disease in high-risk populations. This prospective diagnostic study included participants at high risk of TB infection (TBI) or progression to TB disease at 10 US sites between 2012 and 2020. Participants of any age who had close contact with a case patient with infectious TB, were born in a country with medium or high TB incidence, had traveled recently to a high-incidence country, were living with HIV infection, or were from a population with a high local prevalence were enrolled from July 12, 2012, through May 5, 2017. Participants were assessed for 2 years after enrollment and through registry matches until the study end date (November 15, 2020). Data analysis was performed in June 2023. At enrollment, participants were concurrently tested with 2 IGRAs (QFT-GIT from Qiagen and TSPOT from Oxford Immunotec) and the TST. Participants were classified as case patients with incident TB disease when diagnosed more than 30 days from enrollment. Estimated positive predictive value (PPV) ratios from generalized estimating equation models were used to compare test performance in predicting incident TB. Incremental changes in PPV were estimated to determine whether predictive performance significantly improved with the addition of a second test. Case patients with prevalent TB were examined in sensitivity analysis. A total of 22 020 eligible participants were included in this study. Their median age was 32 (range, 0-102) years, more than half (51.2%) were male, and the median follow-up was 6.4 (range, 0.2-8.3) years. Most participants (82.0%) were born outside the US, and 9.6% were close contacts. Tuberculosis disease was identified in 129 case patients (0.6%): 42 (0.2%) had incident TB and 87 (0.4%) had prevalent TB. The TSPOT and QFT-GIT assays performed significantly better than the TST (PPV ratio, 1.65 [95% CI, 1.35-2.02] and 1.47 [95% CI, 1.22-1.77], respectively). The incremental gain in PPV, given a positive TST result, was statistically significant for positive QFT-GIT and TSPOT results (1.64 [95% CI, 1.40-1.93] and 1.94 [95% CI, 1.65-2.27], respectively). In this diagnostic study assessing predictive value, IGRAs demonstrated superior performance for predicting incident TB compared with the TST. Interferon-γ release assays provided a statistically significant incremental improvement in PPV when a positive TST result was known. These findings suggest that IGRA performance may enhance decisions to treat TBI and prevent TB.

Tuberculin skin test result detection method based on CSN-II and improved OTSU method

The tuberculin skin test (TST) is an intradermal test used to diagnose Type IV hypersensitivity reactions caused by Mycobacterium tuberculosis infection. Segmentation of TST result images provides a foundation for large-scale tuberculosis screening and auxiliary diagnosis. This paper presents a specialized method for identifying TST results. Initially, a clustering approach is employed to reduce pixel complexity, followed by a linear transformation using CSN-II to enhance the original RGB space with robust color space properties. Subsequently, high-probability pixel points are located, and their Gaussian kernel convolution range is determined using the Bhattacharyya Distance. Through convolution and iterative feature amplification, the target characteristics are progressively enhanced. Finally, an improved OTSU method is proposed for segmenting TST result images. In this method, an adaptive entropy threshold is utilized to reduce the search range of the OTSU method, enhancing the relative contrast between the target and the background. Moreover, a weighted adjustment is applied to the obtained OTSU threshold to prevent drift towards backgrounds with larger intra-class variances. Experimental results demonstrate that the proposed method achieves higher segmentation accuracy and robustness in TST result image segmentation compared to traditional OTSU methods and other improved approaches, such as the neighborhood valley-emphasis method, logarithmic OTSU, and weighted OTSU, Finally, we calculate a relative value is calculated by dividing the remaining number of segmented pixels by the total number of pixels, we then classify the results based on the relative value and in reference to medical diagnostic standards our method is intended to establish an algorithmic basis for rapid screening and classification of tuberculosis on a large scale.

Prevalence of Latent Tuberculosis Infection Among Nurses Working in Critical Areas at a Tertiary Care Hospital in Riyadh, Saudi Arabia.

Introduction Tuberculosis is a critical health issue worldwide.Most infected persons are asymptomatic and categorized as having a latent tuberculosis infection (LTBI). Healthcare workers (HCWs) are more prone to being infected with tuberculosis and should be enrolled in a screening program for early detection. Objectives The study aims to estimate the prevalence of LTBI among nurses working in critical areas which include adult intensive care units, pediatric intensive care units, emergency departments, oncology departments, dialysis departments, tuberculosis labs, isolation rooms, and cardiac center intensive care units. Methods A record-based cross-sectional survey measured the prevalence of LTBI among nurses working in critical areas at Prince Sultan Military Medical City (PSMMC), Riyadh, Saudi Arabia. We reviewed the occupational health records of all nurses working in critical areas from June 1, 2021, to June 1, 2022. We recorded the data reviewed throughout the year in the Occupational Health Department at PSMMC. We excluded all participants with previously documented positive tuberculin skin test (TST) from the study. We analyzed the sociodemographic data, working years, working location, job title, and TST results. Results We included a total of 771 out of 2025 nurses in this study. Participants were mostly women (88%) and in the 26-35-year age group (67.7%). Most of the participants were originally from the Philippines (66.3%). The overall LTBI prevalence among nurses was 34.5%. The highest prevalence of LTBI was among nurses working in the cardiac intensive care unit (53.5%), and the lowest prevalence was among nurses working in the isolation department (8.9%; p-value <0.0001). Those who worked more in the hospital were significantly more infected with LTBI (p-value <0.04). Conclusion LTBI remains a significant health risk worldwide andin the Middle East as well as among HCWs. This underscores the necessity of comprehensive pre-hiring screening, annual screening, infection control protocols, and active management of HCWs with LTBI.

QuantiFERON Gold-In-Tube for the diagnosis of mycobacterial tuberculosis infection in children under 5 years of age: A systematic review and meta-analysis.

Previous meta-analysis regarding the performance of QuantiFERON Gold-In-Tube in children have yielded contrasting results. Emerging data in children younger than 5 years of age necessitates a new analysis. Systematic searches were conducted of MedLINE, EMBASE and Cochrane databases between 1998-2023. Pooled estimates of sensitivities and specificities of QFT-GIT compared to tuberculin skin test (TST) were calculated. The Kappa (k) coefficient was calculated for each study to determine the degree of congruence between TST and QFT-GIT results. Studies including patients co-infected with HIV or other immune compromising conditions or those treated with anti-tubercular treatment were excluded. Seventeen studies (4335 patients) were included in quantitative analysis. All studies were conducted in middle to high income countries. They were conducted across 14 countries and 4 studies in countries with high TB incidence. The pooled sensitivity, specificity and DOR were 0.45 (0.42-0.48), 0.96 (0.96-0.97) and 18.84 (7.33-48.41) respectively. The ability of QFT-GIT to discriminate with disease and no disease was "good" as demonstrated by a summary receiver operating characteristic curve with area under curve of 0.7812. The average Kappa (k) co-efficient was 0.501 with a wide variety of values between studies (0.167 to 0.800). The findings of this meta-analysis support the judicious use of QFT-GIT in children 5 years and under, with caution as a sole test to exclude Tuberculosis in this age group. The heterogeneity and methodological quality of diagnostic studies limits the generalisability of results.

Enhancing bovine tuberculosis screening at Dhaka city in Bangladesh: Integrating gamma interferon blood test as ancillary testing with tuberculin skin test

Tuberculin skin test (TST) is the standard method for screening of bovine tuberculosis (bTB). However, gamma interferon blood test has been introduced in the bTB control program as an ancillary testing with TST in many countries of the world. The objective of this study was to recommend this screening test as an ancillary testing with TST for field application in Bangladesh. In this study 577 cattle of different age, sex and breeds from twenty nine (29) cattle herds were examined to determine skin response against bTB through single intradermal comparative tuberculin test (SICTT) that comprised of positive (n = 81), inconclusive (n = 44) and negative (n = 452) animals. Of which 74 animals that included positive (n = 63), inconclusive (n = 8) and negative (n = 3) animals were taken under this study. Blood samples were collected in heparinized tube and stimulated overnight with bovine and avian purified protein derivatives (PPDs) for the secretion of gamma interferon, and measured via sandwich ELISA. Cohen’s kappa statistics was performed for the evaluation of agreement between the two tests. The agreement obtained between two tests was fair (Kappa agreement, K = 24.0%, 95% CI = 16.9−30.5%, P = 0.037). Of positive (n = 63), inconclusive (n = 8) and negative (n = 3) status of animals at SICTT, 82.54% (n = 52), 62.50% (n = 5), and 33.33% (n = 1) were found to be bTB positive respectively through this ancillary test. This test notably corroborates to TST result. A considerable number of inconclusive TB status animals were found to be positive through this gamma interferon assay. Therefore, this test could be used as an ancillary test with TST to maximize the proportion of bTB estimation in the infected cattle herd for early detection of zoonotic tuberculosis in Bangladesh before transmission at the animal-human interface.

Prevalence and incidence of tuberculosis infection among healthcare workers in chest diseases hospitals, Bangladesh: Putting infection control into context.

Healthcare workers (HCWs) are at increased risk of tuberculosis infection (TBI). We estimated the prevalence and incidence of TBI and risk factors among HCWs in Bangladeshi hospitals to target TB infection prevention and control (IPC) interventions. During 2013-2016, we conducted a longitudinal study among HCWs in four chest disease hospitals. At baseline, we administered a questionnaire on sociodemographic and occupational factors for TB, tuberculin skin tests (TST) in all hospitals, and QuantiFERON ®-TB Gold in-Tube (QFT-GIT) tests in one hospital. We assessed factors associated with baseline TST positivity (induration ≥10mm), TST conversion (induration increase ≥10mm from baseline), baseline QFT-GIT positivity (interferon-gamma ≥0.35 IU/mL), and QFT-GIT conversion (interferon-gamma <0.35 IU/mL to ≥0.35 IU/mL). We included factors with a biologically plausible relationship with TBI identified in prior studies or having an association (p = <0.20) in the bivariate analyses with TST positivity or QFT-GIT positivity in multivariable generalized linear models. The Kaplan-Meier was used to estimate the cumulative TBI incidence rate per 100 person-years. Of the 758 HCWs invited, 732 (97%) consented to participate and 731 completed the one-step TST, 40% had a positive TST result, and 48% had a positive QFT-GIT result. In multivariable models, HCWs years of service 11-20 years had 2.1 (95% CI: 1.5-3.0) times higher odds of being TST-positive and 1.6 (95% CI 1.1-2.5) times higher odds of QFT-GIT-positivity at baseline compared with those working ≤10 years. HCWs working 11-20 years in pulmonary TB ward had 2.0 (95% CI: 1.4-2.9) times higher odds of TST positivity, and those >20 years had 2.5 (95% CI: 1.3-4.9) times higher odds of QFT-GIT-positivity at baseline compared with those working <10 years. TBI incidence was 4.8/100 person-years by TST and 4.2/100 person-years by QFT-GIT. Females had 8.5 (95% CI: 1.5-49.5) times higher odds of TST conversion than males. Prevalent TST and QFT-GIT positivity was associated with an increased number of years working as a healthcare worker and in pulmonary TB wards. The incidence of TBI among HCWs suggests ongoing TB exposure in these facilities and an urgent need for improved TB IPC in chest disease hospitals in Bangladesh.

Tuberculin skin testing and QuantiFERON™-TB Gold Plus positivity among household contacts in Vietnam.

TB infection (TBI) is diagnosed using the technique-dependent tuberculin skin test (TST) or costly, more accurate interferon-gamma release assays. The TST (⩾10 mm) threshold was indicated by previous research among household contacts in Vietnam, but routine implementation with a different tuberculin reagent showed unexpectedly low TST positivity. TST (⩾5 mm and ⩾10 mm) results were compared to QuantiFERON™-TB Gold Plus (QFT) results in household contacts during community campaigns in 2020 and 2021. This was a cross-sectional multi-center implementation study. Among 1,330 household contacts in 2020, we found a TBI prevalence of 38.6% (QFT), similar to TST ⩾5 mm (37.4%) and higher than TST ⩾10 mm (13.1%). QFT+/TST+ was higher for TST ⩾5 mm (20.7%) than TST ⩾10 mm (9.4%). QFT was not discordant with TST ⩾5 mm (McNemar's test = 0.6, P = 0.5) but was discordant with TST ⩾10 mm (McNemar's test = 263.9, P < 0.01). Older age and Southern region increased odds for positive TST ⩾5 mm and QFT with weaker associations for TST ⩾10 mm. Agreement and discordance were similar in 2021 for 1,158 household contacts. Tuberculin reagents affect TST positivity rates. High TB burden countries should monitor reliability of TBI diagnosis, including tuberculin potency, cold chain, and TST technique to optimize eligibility for TB preventive treatment.

Pregnancy and neonatal outcomes in infertile patients with positive tuberculin skin test results

Research questionDo infertile women with positive tuberculin skin test (TST) results have a higher risk of adverse pregnancy outcomes after IVF or intracytoplasmic sperm injection and embryo transfer (ICSI–ET) and does preventive anti-tuberculosis treatment applied to infertile women with positive TST results before IVF/ICSI–ET affect pregnancy and neonatal outcomes? DesignThis was a retrospective cohort analysis of 6283 infertile women who underwent IVF/ICSI–ET treatment for the first time at the Reproductive Hospital affiliated to Shandong University from November 2016 to September 2022. None of the participants had prior tuberculosis or active tuberculosis. According to their TST results, 5947 patients who had never received preventive anti-tuberculosis treatment were divided into a TST-positive group (1704 cases) and a TST-negative group (4243 cases). A total of 504 patients with TST (+++) results (using the 20 mm sclerosis threshold) were divided into a treated TST (+++) group (336 cases) and an untreated TST (+++) group (168 cases) according to whether they received preventive anti-tuberculosis treatment before IVF/ICSI–ET. The outcome measures were pregnancy outcomes and neonatal outcomes. ResultsThere were no significant differences in pregnancy or neonatal outcomes between the TST-positive group and the TST-negative group (P > 0.05). In the TST (+++) group, there were no significant differences in pregnancy or neonatal outcomes between the treated TST (+++) group and the untreated TST (+++) group (P > 0.05). ConclusionsFor infertile women undergoing IVF/ICSI–ET without prior tuberculosis or active tuberculosis, positive TST results and preventive anti-tuberculosis treatments prior to IVF/ICSI–ET do not affect pregnancy or neonatal outcomes.

LTBI-negative close contacts of tuberculosis are more likely to develop the disease: enlightenment and lessons from a cluster outbreak.

Tuberculosis (TB) prevention and control among groups living together, such as students, workers, older adults in nursing homes, and prisoners, present many challenges due to their particular age and environmental factors, which can make them more susceptible to TB clusters with significant societal impact. This study aimed to evaluate a TB cluster outbreak epidemic in a university and provide suggestions for improving TB control strategies for groups living together. Pulmonary TB screening and close-contact investigation were conducted using acid-fast staining, sputum culture, GeneXpert testing, tuberculin skin testing (TST), interferon-gamma release assay (IGRA), and chest computed tomography (CT). GraphPad Prism 9.5.1 was utilized for data analysis. Collected epidemic data were comprehensively analyzed by rate comparison. The TB cluster outbreak epidemic was identified with an index case confirmed positive. The initial screening was conducted on potential close contacts of the index case, and the TST's positive rate (diameter ≥ 5 mm) and strong positive rate (diameter ≥ 15 mm) among these close contacts were 65.60% (21/32) and 34.40% (11/32), respectively. Moreover, the latent TB infection (LTBI) rate (diameter ≥ 10 mm) was 43.75% (14/32), and the IGRA's positive rate was 9.30% (3/32). Chest CT scans did not reveal any abnormalities. Surprisingly, 5 of the close contacts developed active TB in the second screening, accompanied by changes from negative to positive TST and/or IGRA results, after 3 months of follow-up. Accordingly, we expanded the screening scope to include another 28 general contacts. We found that the positive rate (78.00%, 25/32), strong positive rate (50.00%, 16/32), and LTBI rate (62.50%, 20/32) of the 32 close contacts were significantly higher than those of the additional general contacts (28.00%, 8/28; 14.3%, 4/28; 25.00%, 7/28), as indicated by p < 0.05. In the event of an epidemic TB outbreak, it is essential to rapidly identify the source of infection and initiate timely screening of close contacts. The initial screening should be focused on individuals without LTBI, who are at higher risk of developing TB. In purified protein derivative-negative individuals living in groups, additional vaccination or revaccination with Bacille Calmette-Guérin may help prevent cluster outbreaks of TB.

TUBERCULIN SKIN TEST AND INTERFERON-γ RELEASE ASSAY ON THE DIAGNOSIS OF TUBERCULOUS SPONDYLITIS

Highlights TST and IGRA have a significant correlation with the diagnosis of patients with Tuberculous Spondylitis. Various factors may affect the results of TST and IGRA. Thus, the use of TST and IGRA can be adjusted according to the condition of the hospital, the availability of diagnostic tools, the health worker’s physical examination results, and the patient's medical history. Abstract Background: Tuberculous spondylitis or Pott’s disease is extrapulmonary tuberculosis that is still a concern to health workers because of the broad spectrum of its clinical symptoms. Delay in diagnosis is very common in this disease. Therefore, its diagnostic tool needs to be thoroughly reviewed to determine its effectiveness. The diagnostic tools studied in this study were Tuberculin Skin Test (TST) and Interferon-γ Release Assay (IGRA). Objective: To analyze the role of TST and IGRA as diagnostic tools for the diagnosis of tuberculous spondylitis. Material and Method: This study used a systematic review method to analyze topic-related kinds of literature written in English and Indonesian found on PubMed, Scopus, ProQuest, and Web of Science databases. The literature screening process was carried out based on the PRISMA 2020 Guidelines. Result: Sixteen types of literature were included for a total of 116 patients. TST was detected positive in 45 (63%) and negative in 21 (30%) of a total of 66 patients with Pott’s disease. IGRA was detected positive in 51 (77%), negative in 8 (12%), and indeterminate in 2 (3%) of a total of 61 patients with Pott’s disease. Conclusion: TST and IGRA results significantly correlate with the diagnosis of tuberculous spondylitis. Both tests are still relevant for use in the diagnosis of the disease. IGRA and TST are used according to the needs of health workers and patients’ health backgrounds.

Tuberculosis contact-tracing results in childhood: a retrospective study in a tertiary-care children’s hospital in Turkey

ABSTRACT Background Smear-positive adults with tuberculosis are the main source of childhood tuberculosis. The evaluation of children exposed to tuberculosis and determination of the disease stages are the cornerstones of managing childhood tuberculosis. Aim To determine the frequency of tuberculous contact, latent tuberculosis infection and tuberculosis disease in children who were in contact with smear-positive adults. Methods This is a single-centre, retrospective study. The medical records of children exposed to tuberculosis (<18 years old) between 2014 and 2018 were investigated. After diagnosing the index cases, the children were referred to the hospital. To identify the children in contact with adults with tuberculosis, a careful medical history, demographic features and physical examination, tuberculin skin test, postero-anterior and lateral chest radiographs, and, if necessary, chest computed tomography and microbiological tests were undertaken. The children’s final diagnosis, treatment regimens and follow-up were documented. The sensitivity, specificity and positive and negative predictive values, tuberculin skin test and chest radiograph imaging were assessed and compared with computed tomography results. Results A total of 150 paediatric patients were exposed to 88 index cases. These were fathers in 29.3% of cases and mothers in 10% of cases. Of the children, 131 (87.3%) were asymptomatic, and physical examination was normal in all children, apart from one who had respiratory symptoms. The tuberculin skin test results were positive in 60 (43%) patients and chest radiograph was abnormal in 100 (66%) children. Findings were consistent with tuberculosis in 34 (40%) of the 84 patients who underwent computed tomography. Fifty (38.5%) of the remaining children were defined as having been in contact with a case of tuberculosis, 41 (31.5%) had latent tuberculous infection and 39 (30%) had tuberculosis disease. Conclusion Pulmonary tuberculosis is asymptomatic in most children but with meticulous use of computed tomography it can be detected in asymptomatic children who have had close contact with tuberculosis. Abbreviation: AFB: acid-fast bacilli; AUC: area under the curve; BCG: bacillus Calmette-Guérin; CI: confidence interval; CT: computed tomography; CXR: chest radiograph; HIV: human immunodeficiency virus; ICD-10: International Classification of Diseases 10; LTBI: latent tuberculosis infection; MDR-TB: multi-drug-resistant tuberculosis; NPV: negative predictive value; PCR: polymerase chain reaction; PPV: positive predictive value; ROC: receiver operating characteristics; SD: standard deviation; TB: tuberculosis; TST: tuberculin skin test; XDR-TB: extensively drug-resistant tuberculosis.

Postvaccination immune responses and risk of primary total hip arthroplasty—A population-based cohort study

To investigate the relationship between individual postvaccination immune responses and subsequent risk of total hip arthroplasty (THA) due to idiopathic osteoarthritis (OA) or rheumatoid arthritis (RA). Results of tuberculin skin tests (TSTs) following the Bacille Calmette-Guerin (BCG) vaccination were used as a marker of individual immune responses. TST results from the mandatory mass tuberculosis screening program 1948-1975 (n=236 770) were linked with information on subsequent THA during 1987-2020 from the Norwegian Arthroplasty Register. The multivariable Cox proportional hazardregression was performed. A total of 10 698 individuals received a THA during follow-up. In men, there was no association between TST and risk of THA due to OA (Hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.92-1.12 for positive versus negative TST and HR 1.06, 95% CI 0.95-1.18 for strong positive vs negative TST), while the risk estimates increased with increasingly restrictive sensitivity analyses. In women, there was no association with THA due to OA for positive versus negative TST (HR 0.98, 95% CI 0.92-1.05), while a strong positive TST was associated with reduced risk of THA (HR 0.90, 95% CI 0.84-0.97). No significant associations were observed in the sensitivity analysis for women or for THA due to RA. Our results suggestthat an increased postvaccination immune response is associated with a nonsignificant trend of increased risk of THA among men and a decreased risk among women, although risk estimates were small.